Today, over 35 million Americans are over the age of 65. Within the next 30 years this number is likely to double, putting more and more people at increased risk of neurodegenerative disease. Over the past several decades, numerous small- and large-molecule products have been developed for treatment of neurodegenerative diseases with mixed success. When administered systemically in vivo, the blood-brain barrier (BBB) inhibits their delivery to the regions affected by those diseases. Safe and localized opening of the BBB has been proven to pose an equally significant challenge. Focused Ultrasound (FUS), in conjunction with microbubbles, remains the sole technique that can induce localized BBB opening noninvasively. Previously, our group has demonstrated that neuroprotection and neurorestoration in the dopaminergic neurons in the nigrostriatal pathway at the early stages of disease can be induced through ultrasound-mediated drug delivery. In this study, we will develop and optimize a theranostic ultrasound system that can simultaneously induce and map the BBB opening in mice and primates in vivo. As a secondary objective, we will determine whether this new BBB opening systems are sufficient to induce BBB at sufficient levels to induce neuroprotection and neurorestoration through gene delivery in mice and NHP for the treatment of motor symptoms in Parkinsonian models associated with early- stage PD. The multi-disciplinary team assembled encompasses all critical specialty areas such as ultrasound and microbubble engineering, neuroscience as well as MRI, PET and fluorescence brain imaging, behavioral testing and mouse model development as well as clinical specialty in movement disorders.This study will thus determine whether theranostic FUS can have a more widespread impact by being implemented in diagnostic imaging scanners and efficacious enough for the treatment of early stage Parkinson?s in conjunction with gene delivery.